Following each 7-day IH protocol, mean HVR was significantly (p < 0.05) increased by 67% and 49% (for LDIH and SDIH, respectively). One week post IH, HVR values were not different from pre-values. HCVR was increased significantly by the LDIH protocol by 44.1% (p < 0.01) and remained elevated by 41.5% at 7 days post (p < 0.01). The changes following the SDIH protocol were smaller (20.7% and 13.5%, at 1 and 7 days post IH, respectively) and not significant. The HCVR remained elevated 7 days following IH (26.7%, p < 0.01). In both the hyperoxic and hypoxic modified rebreathing tests, the CO2 sensitivity was unchanged by either intervention. In hypoxia, the CO2 threshold was significantly reduced following both protocols (p < 0.05). LDIH reduced the threshold by 1.60mmHg, whereas following SDIH it was reduced by 1.98mmHg. Under hyperoxic conditions, LDIH reduced the CO2 threshold by 2.06 mmHg, and SDIH caused a reduction of 2.53 mmHg. There were no significant differences between the two IH protocols for any of the above measures. A 7-day intermittent hypoxic protocol consisting of daily 60-minute exposures to normobaric poikilocapnic hypoxia caused increases in HVR and HCVR. This protocol caused a left-shift in the CO2 threshold but no change in CO2 sensitivity by the modified rebreathing protocol. Neither protocol proved superior in effecting these changes in the resting control of breathing.

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ObjectiveSildenafil is a pulmonary vasodilator that may reduce the decrement in endurance performance in moderate hypoxia. We assessed the efficacy of sildenafil to improve performance in hypoxia.Data sources/eligibility CriteriaWe systematically searched electronic databases (until August 2018) for randomised trials comparing sildenafil with placebo. We also examined the effect of sildenafil on pulmonary artery pressure (PAP), cardiac output (CO) and pulse oxygen saturation (SPO2) compared with placebo in hypoxia. Fourteen studies were included; 210 subjects received sildenafil 40, 50 or 100 mg/day.ResultsSildenafil showed a large effect for decreasing PAP during exercise and at rest, a small effect for increasing CO during exercise and a moderate effect at rest, a moderate effect for increasing SPO2and a small effect for improving performance. In a subgroup analysis, there was no statistically significant difference between 100 and 50 mg sildenafil dose on SPO2. Sildenafil had a moderate effect on increasing SPO2and performance at terrestrial hypobaric altitude but only a small effect on both in normobaric hypoxia. Regression analysis showed that hypoxic dose (PO2) and metabolic rate do not account for a significant portion of the variance in effect size for sildenafil on PAP, CO, SPO2and performance.ConclusionThis meta-analysis indicates that sildenafil reduces PAP, has a moderate to small effect on CO and SPO2, and no effect on performance.

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